Working…
Help guide our efforts to modernize ClinicalTrials.gov.
Send us your comments by March 14, 2020.
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Trial Evaluating the Addition of Nivolumab to Cisplatin-RT for Treatment of Cancers of the Head and Neck (NIVOPOSTOP)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03576417
Recruitment Status : Recruiting
First Posted : July 3, 2018
Last Update Posted : January 18, 2020
Sponsor:
Collaborator:
UNICANCER
Information provided by (Responsible Party):
Groupe Oncologie Radiotherapie Tete et Cou

Brief Summary:
The purpose of this study is to determine the efficacy of nivolumab + cisplatin-RT relative to standard of care (SOC) cisplatin-RT alone, using the disease-free survival (DFS by investigator imaging assessment) as primary endpoint )

Condition or disease Intervention/treatment Phase
Squamous Cell Carcinoma of Head and Neck Drug: Cisplatin Drug: Nivolumab Radiation: RT Phase 3

Detailed Description:

This open-label, randomized, controlled, multicenter phase III study will include 680 patients who have been operated for their LA SCCHN and exhibiting extra capsular extension (ECE) and/or positive margins (high risk). Subjects will be randomized (1:1) to receive post-operative concomitant cisplatin-RT with or without nivolumab.

The study is designed with the general objective of demonstrating that treatment with nivolumab in combination with 3 cycles of cisplatin during RT is more efficient and not more toxic than the SOC 3 cycles of cisplatin during RT.

Stratification will be based on the P16 status (immunohistochemistry assay on surgical sample). Two classes: Oropharyngeal Cancer (OPC) p16 positive versus OPC p16 negative or not OPC.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 484 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase III Randomized Trial of Post-operative Adjuvant Nivolumab and Concomitant Chemo-radiotherapy in High-risk Patients With Resected Squamous Cell Carcinoma of Head and Neck
Actual Study Start Date : October 10, 2018
Estimated Primary Completion Date : December 2021
Estimated Study Completion Date : December 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: RT+ cisplatin
100 mg/m2 of cisplatin on days 1, 22,43 of RT
Drug: Cisplatin
Intravenous

Radiation: RT
IMRT 66 Gy / 6.5 weeks
Other Name: IMRT

Experimental: RT+ cisplatin + nivolumab
  • 360 mg of nivolumab 3 weeks before RT-Cisplatin
  • 360 mg of novolumab on days 1, 22,43 of -RT-cisplatin
Drug: Cisplatin
Intravenous

Drug: Nivolumab
Intravenous

Radiation: RT
IMRT 66 Gy / 6.5 weeks
Other Name: IMRT




Primary Outcome Measures :
  1. Disease free survival [ Time Frame: 3 years after the end of RT ]
    The time between the date of randomization and the date of first recurrence or death (of any cause) whichever occurs first


Secondary Outcome Measures :
  1. Overall survival [ Time Frame: 60 months after the end of treatment ]
    Time between the date of randomization and death

  2. Acute toxicity [ Time Frame: During treatment and until 90 months after the end of RT ]
    The maximal grade of each toxicity observed during radiotherapy plus concomitant treatment graded according to the NCI CTCAE v5.0

  3. Late toxicity [ Time Frame: 1 to 5 years after radiotherapy ]
    Late toxicity from 1 year to 5 years after radiotherapy will be categorized in three categories (none, grade 1-2, or grade 3-4), and compared between the two arms using generalised linear models for multinomial variables with a cumulative logit link



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 74 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age > 18 and < 75 years
  2. Performance Status (PS) ECOG 0-1 (Appendix 2)
  3. Written informed consent
  4. Recording of alcohol consumption and smoking history
  5. Stage III, stage IV (American Joint Committee on Cancer 7th edition) 38
  6. Oral cavity, oropharynx, hypopharynx or larynx
  7. Squamous cell carcinoma treated by primary surgery
  8. Recovery from the surgical procedure allowing for cisplatin-RT
  9. RT planned within 4 to 8 weeks after surgery
  10. Patient/tumor carrying a high risk of relapse with:

    • extra-capsular extension (ECE),
    • and/or positive margins (R1 or close margin ≤ 1 mm)
  11. Availability of surgical tumour specimen (PD-L1, TILs and immune landscape ...)
  12. For oropharyngeal tumor, known p16 status (by IHC)
  13. Determination of patient ability to receive cisplatin 100 mg/m2 for 3 cycles:

    • Calculated creatinine clearance ≥ 60 mL/min as determined by CKD-EPI method (Cockcroft and Gault or MDRD method allowed)
    • Absolute neutrophil count ≥1 500/μL, platelets ≥100 000/μL, haemoglobin ≥ 10 g/dL, aspartate (AST) and alanine transaminase (ALT) less than 2 times the upper limit of the normal range (ULN), total bilirubin ≤ 1.5 mg/dL, serum albumin >35 g/L
    • Peripheral neuropathy ≤ grade 1
    • Sensorineural hearing loss (confirmed by audiogram)
    • Cardiac function compatible with hyperhydration
    • No administration of prophylactic phenytoin
    • For ppatients aged 71-74 years, PS must be 0 and fit according to geriatric evaluation

Exclusion Criteria:

  1. Nasopharyngeal, paranasal sinuses, nasal cavity tumours or thyroid cancers
  2. Squamous cell carcinoma involving cervical neck nodes with unknown primary site
  3. Metastatic disease (stage IVc)
  4. Active viral infection (HIV, Hepatitis B/C) or known history of positive test for HIV
  5. Active autoimmune disease
  6. Active immunodeficiency or ongoing immunosuppressive therapy
  7. Active CNS disease
  8. Interstitial lung disease
  9. Active infection
  10. Any prior or current treatment for invasive head and neck cancer. This will include but is not limited to: prior tyrosine kinase inhibitors, any monoclonal antibody, induction chemotherapy, prior RT, or use of any investigational agent
  11. Concurrent treatment with any other systemic anti-cancer therapy that is not specified in the protocol
  12. Concomitant treatment with any drug on the prohibited medication list such as live vaccines. Live vaccines administered more than 30 days before study entry are permitted
  13. History of other malignancy within the last 3 years (exception of in situ carcinoma, thyroid papillary carcinoma, skin carcinomas, localized prostate carcinoma Gleason 6 and in situ breast carcinoma)
  14. Pregnant, breastfeeding patients, and female patients of childbearing potential who are unwilling or unable to use 2 highly effective methods of contraception as outlined in the protocol for the duration of the study and for at least 6 months after the last dose of cisplatin and 7 months after the last dose of nivolumab
  15. Significant disease which, in the judgment of the investigator, as a result of the medical interview, physical examinations, or screening investigations would make the patient inappropriate for entry into the trial
  16. Known hypersensitivity reaction to study drugs
  17. Any social, personal, medical and/or psychologic factor(s) that could interfere with the observance of the patient to the protocol and/or the follow-up and/or the signature of the informed consent
  18. Prior organ transplantation including allogenic stem-cell transplantation
  19. Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months prior to enrollment), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication
  20. Persisting toxicity related to prior therapy or pre-existing conditions (NCI CTCAE v. 4.03 Grade > 1) 39
  21. Other severe acute or chronic medical conditions including colitis, pneumonitis, pulmonary fibrosis or psychiatric conditions including active suicidal ideation; or laboratory abnormalities that may increase the risk associated with study participation and, in the judgment of the investigator, would make the patient inappropriate for entry into this study
  22. Concurrent enrolment in another clinical trial using an investigational anti-cancer treatment within 28 days prior to the first dose of study treatment

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03576417


Contacts
Layout table for location contacts
Contact: Jean BOURHIS, Pr (0)21 314 46 66 ext +41 jean.bourhis@chuv.ch
Contact: Gabriel WAKSI (0)785 293 799 ext +33 gabriel.waksi@gortec.fr

Locations
Layout table for location information
France
Centre Antoine Lacassagne Recruiting
Nice, France, 06189
Contact: Joël GUIGAY, MD    04 92 03 15 01 ext +33    Joel.Guigay@nice.unicancer.fr   
Sponsors and Collaborators
Groupe Oncologie Radiotherapie Tete et Cou
UNICANCER

Layout table for additonal information
Responsible Party: Groupe Oncologie Radiotherapie Tete et Cou
ClinicalTrials.gov Identifier: NCT03576417    
Other Study ID Numbers: GORTEC 2018-01
First Posted: July 3, 2018    Key Record Dates
Last Update Posted: January 18, 2020
Last Verified: January 2020

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Carcinoma
Carcinoma, Squamous Cell
Squamous Cell Carcinoma of Head and Neck
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Head and Neck Neoplasms
Neoplasms by Site
Cisplatin
Nivolumab
Antineoplastic Agents
Antineoplastic Agents, Immunological